PXD008577-1

PXD008577 is an original dataset announced via ProteomeXchange.

Title	A Peptidomimetic Antibiotic Interacts with the Periplasmic Domain of LptD from Pseudomonas aeruginosa
Description	Gram-negative bacterial infections are causing increasing levels of morbidity due to the rise of resistance to established antibiotics. New antibiotic classes with distinct molecular mode of action are therefore required. Recently, a family of macrocyclic peptidomimetics was discovered that target the outer membrane LPS transport protein LptD to specifically inhibit bacterial growth in Pseudomonas spp. To characterize the interaction of these antibiotics with LptD from P. aeruginosa, we combined photo-crosslinkable peptidomimetics and hypothesis-free mass spectrometry-based proteomics. We provide evidence that the antibiotic cross-links to the periplasmic segment of LptD, containing a ß-jellyroll domain and an N-terminal insert domain that is characteristic of Pseudomonas spp. Binding of the antibiotic to the periplasmic segment of LptD is expected to block LPS transport, consistent with the proposed mode of action and observed specificity of these antibiotics. These insights may prove valuable for the discovery of new antibiotics targeting the LPS transport pathway in other Gram-negative bacteria.
HostingRepository	PRIDE
AnnounceDate	2018-06-21
AnnouncementXML	Submission_2018-06-21_00:11:09.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maik Mueller
SpeciesList	scientific name: Pseudomonas aeruginosa PAO1; NCBI TaxID: 208964;
ModificationList	monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-02 06:19:46	ID requested
⏵ 1	2018-06-21 00:11:10	announced
2	2024-10-22 04:12:40	announced	2024-10-22: Updated project metadata.

Andolina G, Bencze LC, Zerbe K, M, ü, ller M, Steinmann J, Kocherla H, Mondal M, Sobek J, Moehle K, Maloj, č, i, ć G, Wollscheid B, Robinson JA, A Peptidomimetic Antibiotic Interacts with the Periplasmic Domain of LptD from Pseudomonas aeruginosa. ACS Chem Biol, 13(3):666-675(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Gram-negative bacteria, pseudomonas, peptidomimetic antibiotic, Lpt complex, photo crosslinking, DIA, LC-MS/MS, Thermo Q-Exactive Plus, molecular mode of action

Bernd Wollscheid
contact affiliation	Institute of Molecular Systems Biology, Department of Health Sciences and Technology, ETH Zurich, Switzerland
contact email	bernd.wollscheid@imsb.biol.ethz.ch
lab head
Maik Mueller
contact affiliation	ETH Zurich
contact email	maimuell@ethz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008577
     1. Label: PRIDE project
     2. Name: A Peptidomimetic Antibiotic Interacts with the Periplasmic Domain of LptD from Pseudomonas aeruginosa